Exaggerated pulmonary vascular response to acute hypoxia in older men

Abstract

New Findings r What is the central question of this study?Pulmonary arterial pressure is higher in older than younger humans and predicts mortality. It is also increased by acute hypoxia, which causes constriction of the pulmonary vasculature. We asked whether this pulmonary vascular response to hypoxia is greater in older humans. r What is the main finding and its importance?Using Doppler echocardiography in 12 younger (ß20 years old) and nine older men (ß55 years old) exposed to 20 min of moderate isocapnic hypoxia, we demonstrated that older men showed a significantly greater rise in pulmonary arterial pressure during alveolar hypoxia than younger men. Future studies should examine the pathophysiological importance of increased hypoxic pulmonary vasoconstriction with age.Resting pulmonary arterial pressure increases with age in humans. In the general population, higher values are associated with increased mortality, and in common cardiopulmonary diseases, such as congestive heart failure and chronic obstructive pulmonary disease, the presence of pulmonary arterial hypertension portends a worse outcome. Pulmonary arterial pressure increases during alveolar hypoxia, as a consequence of constriction in the pulmonary vasculature. We hypothesized that older men have more vigorous hypoxic pulmonary vasoconstriction than younger men. Twelve younger (20.5 ± 0.5 years old) and nine older men (55.8 ± 2.1 years old) were exposed for 20 min on different days to isocapnic hypoxia (end-tidal P O 2 = 50 mmHg) and isocapnic euoxia (end-tidal P O 2 = 100 mmHg); each was preceded (baseline) and followed by 5 min of isocapnic euoxia. Systolic pulmonary arterial pressure and cardiac output were measured continuously using Doppler echocardiography. Systolic pulmonary arterial pressure was greater during baseline euoxic measurements in older participants (27.8 ± 0.8 versus 24.1 ± 0.7 mmHg, P = 0.001) and also increased more during hypoxia in older participants (15.2 ± 1.3 versus 9.6 ± 0.9 mmHg, P = 0.011). Cardiac output did not differ between the two groups during baseline measurements (P = 0.60) or hypoxia (P = 0.49). All data are means ± SEM. The increased magnitude of hypoxic pulmonary vasoconstriction demonstrated with age has implications for individuals wishing to ascend to high altitude or travel by air, for those suffering from conditions in which global alveolar hypoxia is a feature and for patients requiring general anaesthesia.

Effect of a day-trip to altitude (2500 m) on exercise performance in pulmonary hypertension: randomised crossover trial

“…The PAP was significantly higher at 2500 m versus 470 m both at rest and at end-exercise along with an increased CO, related to the increased heart rate, and a higher PVR at rest, but not end-exercise as assessed by echocardiography. The higher TRPG and PVR at rest suggests that the effect of HPV was present after >3 h at altitude, which is consistent with existing literature [ 33 , 34 ], although in previous studies PAP remained unchanged by exposing patients with pre-capillary PH to normobaric hypoxia for 20 min [ 12 ] and with consecutive CWRET [ 14 ] which was probably related to the shorter exposure. The similar change of the TRPG and CO with exercise at both altitudes resulted in an unchanged pressure–flow slope during exercise at 2500 m versus 470 m. Since a steeper increase in TRPG/CO slope was linked to worse survival, the similar slope found in our study may be a sign that a short-term exposure to a comparable altitude does not acutely harm the cardiopulmonary system; however, our study was not powered to firmly address safety in PH patients going to altitude [ 16 ].…”

Acute hemodynamic changes by breathing hypoxic and hyperoxic gas mixtures in pulmonary arterial and chronic thromboembolic pulmonary hypertension

“…[17] The HPV arises immediately after exposure to hypoxia. [18] In the current study, acute hypoxia did not change the mPAP, PVR nor CO in PAH/CTEPH patients and controls. The absence of a significant response in these variables may be related to the relatively minor degree of hypoxia corresponding to an altitude of 2600 m that only increased HR but did not induce further changes in hemodynamics.…”

Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

“…Children conceived by assisted reproductive technologies [29,30] and young adults who had transient perinatal hypoxic pulmonary hypertension have been shown to display an augmented PAP increase at high altitude [31]. Further, older men exhibit a significantly greater rise in PAP during acute alveolar hypoxia than younger men [32]. A small study showed that females exhibit a greater pulmonary vascular response to sustained hypoxia than males [33].…”